This clinical trial by Lau et al. aimed to investigate the safety and efficacy of all-oral triple therapy with direct acting antivirals (DAAs) in chronic hepatitis C genotype 1b (GT1b) non-cirrhotic Chinese patients. Twenty six patients were randomly assigned to one of three treatment groups involving combinations of 3 DAAs, which included the NS5B polymerase inhibitor sofosbuvir (SOF), the NS5A inhibitors ledipasvir (LDV) and daclatasvir (DCV), and the NS3/4 protease inhibitors simeprevir (SMV and asunaprevir (ASV).
Response guided therapy was employed in order to continue treatment based on HCV RNA levels at day two of therapy (Rapid Virological Response, RVR). Patients achieving levels <500IU/ml continued treatment until day 21 and were then followed up at 4 and 12 weeks post-treatment (SVR12). Six of twelve patients in Group 1 (SOF+LDV+ASV), 6/6 in Group 2 (SOF+DCV+SMV) and 6/8 in Group 3 (SOF+DCV+ASV) attained the set viral load reduction milestone and continued treatment to day 21. HCV RNA negativity (or a level below the lower limit of quantification) was achieved by all patients in groups 1, 2 and 3, at week1, and weeks 2 and 3 of treatment respectively.
This was maintained in all patients when tested at 4 and 12 weeks of follow-up. Existence of resistance associated variants (RAVs) prior to the start of treatment did not appear to compromise therapy outcome. The authors conclude that triple DAA therapy for 3 weeks is effective in achieving HCV cure in non-cirrhotic Chinese patients with GT1b. Moreover when compared to dual treatment for 8-12 weeks, triple therapy for 3 weeks was cost effective in 61-72% of treated patients.
This proof-of-concept SODAPI study explored RGT to shorten the duration of HCV treatment. The results strongly suggest that administration of potent triple regimens containing NS3, NS5A and NS5B HCV-inhibitors leads to RVR (plasma HCV RNA < 500 IU/mL) within 2 days in two-thirds of non-cirrhotic HCV GT 1b-infected subjects. 100% of subjects with RVR and had treatment for 3 wks, achieved SVR12,with excellent adherence and tolerability. Future studies exploring this RGT concept are recommended to reduce duration of therapy, cut drug costs, and to significantly improve accessibility and adherence.
Lau et al., Poster LB-23, American Association for the Study of the Liver meeting, 2015.